Longitudinal follow-up of the asthma status in a French-Canadian cohort.

Asthma affects 340 million people worldwide and varies in time. Twenty years ago, in Canada, the Saguenay-Lac-Saint-Jean asthma family cohort was created to study the genetic and environmental components of asthma. This study is a follow-up of 125 participants of this cohort to explore the appearance, persistence, and progression of asthma over 10-20 years. Participants answered a clinical standardized questionnaire. Lung function was assessed (forced expiratory volume in 1 s, forced vital capacity, bronchial reversibility, and methacholine bronchoprovocation), skin allergy testing was performed, blood samples were obtained (immunoglobulin E, white blood cell counts) and phenotypes were compared between recruitment and follow-up. From the participants without asthma at recruitment, 12% developed a phenotype of adult-onset asthma with the presence of risk factors, such as atopy, high body mass index, and exposure to smoking. A decrease of PC20 values in this group was observed and a decrease in the FEV1/FVC ratio in all groups. Also, 7% of individuals with asthma at recruitment developed chronic obstructive pulmonary disease, presenting risk factors at recruitment, such as moderate-to-severe bronchial hyperresponsiveness, exposure to smoking, and asthma. This study allowed a better interpretation of the evolution of asthma. Fine phenotypic characterization is the first step for meaningful genetic and epigenetic studies.

Accurate molar masses of cellulose for the determination of degradation rates in complex paper samples.

Complex cellulosic samples are often difficult to analyse with size-exclusion chromatography. The strong molecular associations of hemicelluloses and lignin with cellulose produce multimodal molar mass distributions (MMD) that are difficult to interpret. More reliable ways of calculating the molar masses of cellulose are thus necessary. This is particularly relevant when studying the kinetics of paper degradation, as the number average molar mass is the most precise indicator. In this study various data handling methods based on the deconvolution of bimodal and multimodal MMDs of complex cellulosic samples after SEC-MALS-DRI analysis are examined in order to propose more accurate paper degradation rates. Two deconvolution methods, which do or do not rely on polymer calibration curves were developed and were applied to several kraft and groundwood pulp papers unaged and hygrothermally aged. The deconvolution methods are discussed and evaluated in light of calculated cellulose activation energies, degradation rates and paper usable lifetime predictions.

Benefits of low-dose inhaled fluticasone on airway response and inflammation in mild asthma.

RATIONALE: Current guidelines suggest that asthma should be controlled with the lowest dose of maintenance medication required. OBJECTIVES: To evaluate the effects of a low dose of inhaled corticosteroid compared to a placebo, on airway inflammation and responsiveness in patients with mild symptomatic asthma. METHODS: In this randomized double-blind, placebo-controlled, parallel group study, we looked at the influence of inhaled fluticasone propionate 250 microg/day for 3 months followed by 100 microg/day for 9 months on airway inflammation and methacholine responsiveness in non-smoking subjects with mild allergic asthma. Subjects were evaluated at baseline and 3, 6, 9 and 12 months after treatments; a 2-week evaluation of respiratory symptoms and peak expiratory flow measurements was done before each visit. RESULTS: Fifty-seven subjects completed the 3-month study period. Airway responsiveness, expressed as the PC20 methacholine, increased by 0.27 and 1.14 doubling concentrations, respectively, in placebo-treated (n=33) and in fluticasone-treated (n=24) asthmatic subjects (p=0.03). An additional improvement in PC20 up to 2.16 doubling concentrations was observed in the fluticasone-treated group during the 9-month lower-dose treatment (p=0.0004, end of low-dose period compared with placebo). Sputum eosinophil counts decreased after 3 months of fluticasone 250 microg/day compared with placebo (p<0.0001) and remained in the normal range during the 9-month lower-dose treatment. Respiratory symptoms and peak expiratory flows did not change significantly throughout the study in both groups. CONCLUSION: In mild asthma, keeping a regular minimal dose of ICS after asthma control has been achieved, may lead to a further reduction in airway responsiveness and keep sputum eosinophil count within the normal range.

Fatigue and daytime sleepiness in patients with myotonic dystrophy type 1: to lump or split?

We assessed the relationship and clinical correlates of fatigue and Excessive Daytime Sleepiness (EDS) in 200 myotonic dystrophy type 1 (DM1) patients by means of questionnaire and neuropsychological evaluation. Fatigue levels were higher in patients with EDS and daytime sleepiness levels higher in patients with excessive fatigue. However, EDS without fatigue was rarely observed. Also, DM1 patients with fatigue (with or without EDS) showed greater muscular impairment, CTG repeats, abnormalities regarding personality, depressive symptoms and lower health-related quality of life (HRQoL) than patients without these symptoms. These findings do not readily support the contention that fatigue and EDS constitute distinct clinical manifestations in DM1. Clinicians should systematically evaluate both symptoms since fatigue and EDS have a greater impact on HRQoL than fatigue alone. However, specific rating scales for fatigue in DM1 have yet to be devised.

Clinical features and airway inflammation in mild asthma versus asymptomatic airway hyperresponsiveness.

RATIONALE: We still do not know why some subjects with airway hyperresponsiveness (AHR) experience no respiratory symptoms. OBJECTIVES: Our aim was to compare pulmonary function, perception of bronchoconstriction, and airway inflammation in atopic subjects with mild recently diagnosed (<5 years, n=30) or longer-standing (5 years or more, n=30) symptomatic asthma in comparison with atopic subjects with asymptomatic AHR (n=27). METHODS: All subjects had measurements of expiratory flows, PC(20) methacholine, perception of breathlessness and induced sputum cell differential, eosinophil cationic protein and alpha(2)-macroglobulin levels. RESULTS: Compared with the other groups, PC(20) was significantly lower in longer-standing asthma and perception score for breathlessness at 20% fall in FEV(1) was lower in asymptomatic subjects. Markers of airway inflammation were similar in all groups. There were no significant correlations between sputum eosinophils, alpha(2)-macroglobulin and/or eosinophil cationic protein levels and FEV(1), FVC or PC(20) in either group. CONCLUSION: Subjects with mild asthma or asymptomatic AHR are similar in regard to induced sputum markers of airway inflammation. Although perception of bronchoconstriction was slightly lower in asymptomatic subjects, additional factors are probably involved to explain why they report no respiratory symptoms. Further studies are needed to determine why these last are asymptomatic.

Effect of increased diaphragm activation on diaphragm power spectrum center frequency.

Increased transdiaphragmatic pressure, reduced muscle blood flow, and increased duty cycle have all been associated with a reduction in the center frequency (CFdi) of the diaphragm's electrical activity (EAdi). However, the specific influence of diaphragm activation on CFdi is unknown. We evaluated whether increased diaphragm activation would result in a greater decline in the CFdi when pressure-time product (PTPdi) was kept constant. Five healthy subjects performed periods of intermittent quasi-static diaphragmatic contractions with a fixed duty cycle. In separate runs, subjects targeted transdiaphragmatic pressures (Pdi) by performing end-inspiratory holds with the glottis open and expulsive maneuvers at end-expiratory lung volume (EELV). Diaphragm activation and pressures were measured with an electrode array and balloons mounted on an esophago-gastric catheter, respectively. The EAdi, which was 25+/-8%(S.D.) of maximum at EELV, increased to 61+/-8% (P<0.001) when an identical Pdi (averaging 31+/-13 cmH2O) was generated at a higher lung volume (77% of inspiratory capacity). The latter was associated with a 17% greater decline in CFdi (P=0.012). In order to reproduce at EELV, the decrease in CFdi observed at the increased lung volume, a two-fold increase in PTPdi was required. We conclude that CFdi responds specifically to increased diaphragm activation when pressure-time product remains constant.

Exclusion spirometry: an initiative to increase lung function assessment in primary care.

Ongoing spirometry quality standards are difficult to bring into the daily routine of general practice. As a result, spirometry is rarely performed by primary care physicians. A new approach is proposed: exclusion spirometry. Acceptable and reproducible results are sought. However, the goal of the test is to try to reach values within normal limits, even if results do not reach quality standards. Normal results would be sufficient to exclude respiratory impairment, except in asthma. Abnormal results would require further testing in a diagnostic spirometry laboratory. The aim of the initiative is to enhance the compliance of general practitioners in using spirometers for screening.

Sleep complaints in patients with myotonic dystrophy.

The aim of this study was to document the clinical picture of excessive daytime sleepiness (EDS) and of other sleep disturbances, and to study the relationship of daytime sleepiness to anthropometric data, muscular impairment, and CTG trinucleotide repeat expansion in myotonic dystrophy type 1 (DM1). A total of 157 DM1 patients were surveyed using a modified version of the Sleep Questionnaire and Assessment of Wakefulness. Other measurements included muscular impairment rating and the size of the trinucleotide repeat. Factor analysis and reliability estimates were used to produce a daytime sleepiness scale with five items of the questionnaire. Thirty-eight healthy family members were studied as control subjects. It was found that EDS was present in 33.1% of DM1 patients. Severity of daytime sleepiness correlated with the degree of muscular impairment but not with age, gender, body mass index, age at onset of symptoms, duration of illness, and CTG repeat. DM1 patients reported a longer sleep period, a less restorative sleep, and more difficulty falling asleep, being alert in the morning and staying awake after meals than controls, but a similar incidence of narcolepsy auxiliary symptoms. Compared with DM1 patients without EDS, those with EDS reported greater hypnagogic hallucinations, and greater pain associated with nocturnal awakenings and in their legs upon morning awakenings. In sum, both DM1 patients with and without EDS exhibit characteristics of sleep duration and sleepiness comparable with those found in idiopathic hypersomnia. The severity of daytime sleepiness is weakly related to the extent of muscular impairment but not to CTG repeat.